Co-transplantation of exosomes derived from hypoxia-preconditioned adipose mesenchymal stem cells promotes neovascularization and graft survival in fat grafting
Co-transplantation of exosomes derived from hypoxia-preconditioned adipose mesenchymal stem cells promotes neovascularization and graft survival in fat grafting
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缺氧预处理的脂肪间充质干细胞来源的外泌体的共移植促进脂肪移植中的新血管形成和移植物存活
DOI：
10.1016/j.bbrc.2018.02.076
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发表时间：
2018-02-26
影响因子：
3.1
通讯作者：
Han, Yan
中科院分区：
文献类型：
--
作者：
Han, Yu-di;Bai, Yun;Han, Yan
背景：脂肪来源的基质细胞(ADSCs)来源的外切体(ADSC-Exos)是干细胞血管生成潜能的来源。本研究旨在探讨ADSC来源的外切体(ADSC-Exos)对脂肪移植存活的影响。方法：采用裸鼠皮下脂肪移植模型。在移植组织周围注射低氧预适应的ADSC-Exos和ADSC-Exos。脂肪移植标本称重，苏木精-伊红(H&E)染色和免疫组织化学检测。结果：移植后2~8周，ADSC-Exo组和低氧ADSC-Exo组脂肪移植物重量和Perilipin阳性脂肪细胞数均显著高于对照组，其中低氧ADSC-Exo组效果更好(均P<；0.05)。H&E染色显示ADSC-Exos可减轻脂肪移植物周围炎性细胞的浸润。激光多普勒血流仪显示两组ADSC-Exo组移植组织的血流灌注率均高于对照组(均P<0.05)。免疫荧光显示低氧ADSC-Exo组CD31阳性细胞明显多于ADSC-Exo组。体外实验表明，与ADSC-Exo组和对照组相比，ADSC-Exos共移植能显著促进人脐静脉内皮细胞的迁移(12和24 h)和体外毛细血管网络形成(12 H)。结论：ADSC-Exos共移植能有效促进移植物存活、新生血管形成和减轻脂肪移植物的炎症反应。低氧处理可进一步增强ADSC-Exos的有益作用。(C)2018 Elsevier Inc.保留所有权利。
Background: Adipose-derived stromal cells (ADSCs)-derived exosomes (ADSC-Exos) account for the proangiogenic potential of stem cell. This study aimed to investigate the effect of ADSC-derived exosomes (ADSC-Exos) on the survival in fat grafting.Methods: A nude mouse model of subcutaneous fat grafting was adopted. Hypoxic preconditioned ADSC-Exos and ADSC-Exos were injected around the grafted tissue. The fat graft sample was weighed and examined by hematoxylin and eosin (H&E) staining and immunohistochemistry. Laser Doppler flowmetry and CD31 immunofluorescence staining were used to analyze neovascularization.Results: ADSC-Exo and hypoxic ADSC-Exo groups had a significantly higher weight of fat graft and more perilipin-positive adipocytes than the control groups from 2 to 8 weeks after grafting, and the hypoxic ADSC-Exo group had better outcomes (all P < 0.05). H&E staining showed that ADSC-Exos attenuated infiltration of inflammatory cells around the fat grafts. Laser Doppler flowmetry showed that the two ADSC-Exo groups had better blood perfusion in the graft tissue than the control groups (all P < 0.05). Immunofluorescence demonstrated that the hypoxic ADSC-Exo group had significantly more CD31-positive cells than the ADSC-Exo group. In vitro study showed that hypoxic ADSC-Exos treatment significantly increased the migration (at 12 and 24 h) and in vitro capillary network formation (at 12 h) in the human umbilical vein endothelial cells (HUVECs) as compared with the ADSC-Exo group and control group (all P < 0.05).Conclusions: Co-transplantation of ADSC-Exos can effectively promote the survival of graft, neovascularization and attenuated inflammation in the fat grafts. Hypoxia treatment can further enhance the beneficial effect of ADSC-Exos. (C) 2018 Elsevier Inc. All rights reserved.